Comparative efficacy and safety of pharmacologic, laser, and combination therapies for infantile hemangioma: a systematic review and network meta-analysis with evidence certainty assessment.
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INTRODUCTION: Infantile hemangiomas (IH) are the most common childhood vascular tumors, potentially complicated by ulceration and permanent functional or aesthetic sequelae. Current treatments include corticosteroids, β-blockers, and lasers, among others, existing evidence relies predominantly on direct pairwise comparisons. Consequently, the relative benefits and risks across these modalities remain inadequately defined. We conducted a systematic review and network meta-analysis (NMA) evaluating pharmacologic, laser, and combination therapies for IH to establish treatment hierarchies and inform clinical practice and future guidelines. METHODS: Following a PROSPERO-registered protocol (CRD420261388356), we searched PubMed, Embase, the Cochrane Library, and Web of Science from inception to 1 March 2026, for randomized controlled trials comparing various interventions for IH. The primary endpoint was excellent response rate. Secondary outcomes included other response rates, VAS/HAS changes, healing time, treatment emergent adverse events, and recurrence. After independent risk-of-bias assessment (RoB2) and data extraction, we performed a random-effects NMA. Treatments were ranked using SUCRA probabilities, and evidence certainty was appraised via GRADE and CINeMA. RESULTS: The synthesis comprised 25 trials (2044 patients) evaluating 16 distinct interventions. Risk of bias was low in six trials, raised "some concerns" in 14, and high in 5. Overall, the evidence body was of moderate certainty. Regarding the primary endpoint, intralesional bleomycin combined with oral propranolol yielded significantly higher excellent response rates than oral propranolol alone (RR = 1.55, 95% CI 1.28-1.89; high certainty). Topical timolol with intralesional lauromacrogol (RR = 7.98, 95% CI 1.52-41.79) and oral propranolol with corticosteroids (RR = 2.00, 95% CI 1.03-3.88) showed higher excellent response rates, supported by moderate-certainty evidence. No statistically significant differences in adverse-event incidence were detected across evaluated regimens, but the safety data were limited. Oral atenolol was associated with numerically lower recurrence rates compared to oral propranolol, but the difference did not reach statistical significance (RR = 0.64, 95% CI 0.32-1.28; moderate certainty). DISCUSSION: Oral propranolol remains the standard of care for IH. However, our analysis shows that some combination regimens showed favorable efficacy for excellent clinical response. Still, sparse comparative data and low-certainty evidence currently obscure the optimal combination strategy. Defining precise risk-benefit profiles requires rigorous head-to-head trials utilizing uniform outcome measures. SYSTEMATIC REVIEW REGISTERATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261388356; Identifier: CRD420261388356.